Abstract:The emergence of drug-resistant cancer cells together with the toxicity side effect of chemotherapy agents are the major obstacle in cancer treatment. We focused on providing a new pattern of protein-based nanoparticle as drug delivery system. FTH1 is a kind of protein that exist in human body which has high bio-safety while EGFR is overexpressed in many cancer cells and it has been used as therapeutic target for cancer treatment. Thus, we used genetic methods for integrating EGF onto the surface of FTH1 and found out a more simple way to express the fusion chimeric proteins. To enhance the loading capacity, we first inserted a linker containing more sulfydryl sits (cysteine) into EGF-FTH1 and then adopt chemistry way to covalent bonding the doxorubicin to the nanoparticles. It was found that 72 of doxorubicin molecular could be loaded to one nanoparticle, and they could be released from the nanoparticles at pH5.0. In addition, the resulted DOX/EGF-FTH1 nanoparticles with a small size (~12nm) and narrow size distribution could specifically bind and taken up more by the MCF-7/ADR compared to free doxorubicin and doxorubicin loaded non-targeted ferritin-based nanoparticles. These results demonstrate that the DOX/EGF-XCys-FTH1 could be a very promising drug delivery system.